title: Virus-like particles produced in Saccharomyces cerevisiae elicit protective immunity against Coxsackievirus A16 in mice.
abstract: Hand, foot, and mouth disease (HFMD) has caused significant morbidity and mortality in the Asia-Pacific regions, particularly in infants and young children. Coxsackievirus A16 (CA16) represents one of the major causative agents for HFMD, and the development of a safe and effective vaccine preventing CA16 infections has become a public health priority. In this study, we have developed a yeast system for the production of virus-like particles (VLPs) for CA16 by co-expressing P1 and 3CD of CA16 in Saccharomyces cerevisiae. These VLPs exhibit similarity in both protein composition and morphology as empty particles from CA16-infected cells. Immunization with CA16 VLPs in mice potently induced CA16-specific IgG and neutralization antibodies in a dose-dependent manner. IgG subclass isotyping revealed that IgG1 and lgG2b were dominantly induced by VLPs. Meanwhile, cytokine profiling demonstrated that immunization with VLPs significantly induced the secretion of IFN-γ, indicating potent cellular immune response. Furthermore, in vivo challenge experiments showed that passive immunization with anti-VLPs sera conferred full protection against lethal CA16 challenge in neonate mice. Taken together, our data demonstrated that VLPs produced in yeast might have the potential to be further developed as a vaccine candidate against HFMD.
authors.affiliation: Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Hao-Yang
authors.initials: HY
authors.lastname: Li
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Han
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.forename: Yue-Xiang
authors.initials: YX
authors.lastname: Li
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: He
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003384:Coxsackievirus Infections / Q000517:prevention & control; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics* / Q000276:immunology*; D007116:Immunization, Passive / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D058425:Vaccines, Virus-Like Particle / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D012367:RNA, Viral; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines; D007371:Interferon-gamma